Erratum to: One-level step section histological analysis is insufficient to confirm complete pathological response after neoadjuvant chemoradiation for rectal cancer.

Unfortunately, one of the author name was wrongly published in the original publication. The complete correct name should read as follows "Beatriz Camargo Azevedo". The original article was updated.

One-level step section histological analysis is insufficient to confirm complete pathological response after neoadjuvant chemoradiation for rectal cancer.

BACKGROUND: Neoadjuvant chemoradiation therapy (nCRT) for rectal cancer may lead to cure. As we currently lack reliable methods to clinically confirm the absence of disease, some patients undergo radical resection and have pathological complete response (pCR) still undergo surgery. Furthermore, it is uncertain if conventional one-level histopathological analysis is accurate enough to determine complete response. Confirming pCR is essential to determine the prognosis and to consider the patient's inclusion in trials of adjuvant therapy. The aim of this study was to determine whether the current 1-level approach is sufficient to confirm pCR. METHODS: Four hundred and thirty-five patients with rectal cancer who received nCRT followed by radical resection were analyzed. All cases identified as pCR by 1-level step section histological evaluation were reassessed with 3-level step sections and immunohistochemical analysis to verify the presence of residual disease. RESULTS: Out of 435 patients, 75 (17.2%) were staged as ypT0. Of these, 6 had lymph node involvement and 1 had distant metastasis, leaving 68 (15.6%) who had pCR. After the additional step sections, residual tumor was detected in 12 (17.6%) of these 68. The final pCR rate was 12.9%. Distant recurrence was detected in 7.1% of real-pCR patients compared to 16.7% in the false-pCR group (p = 0.291). Sensitivity of clinical assessment for detecting pCR was 35.7%, and the accuracy of 1-section histological evaluation to identify pCR was 82.4%. CONCLUSIONS: Histopathological analysis with 1-level step section is insufficient to determine complete tumor eradication. The 3-level sections methodology revealed residual tumor cells in patients initially classified as ypT0. Further studies with larger sample size are required to verify the clinical relevance of these residual tumor cells. Caution should continue to be applied to watch and wait strategies following nCRT.

Understanding the factors associated with reduction in the number of lymph nodes in rectal cancer patients treated by neoadjuvant treatment.

INTRODUCTION: Rectal cancer patients frequently present with locally advanced disease for which the standard of care includes neoadjuvant chemoradiotherapy followed by total mesorectal excision. Positive lymph nodes are one of the most powerful risk factors for recurrence and survival in colorectal cancer. In the absence of specific rectal guidelines, the literature recommends to the pathologist to optimize the number of rectal lymph nodes (LN) retrieved. We made a literature review in order to identify factors that could potentially affect the number of LN retrieved in specimens of patients with rectal cancer treated by chemoradiotherapy (CRT) followed by total mesorectal excision (TME). RESULTS: Age did not have a significant effect on LN yield. The effect of sex on LN number is not consistent in the literature. Most of the papers did not find a relationship between lower LN obtained and gender. Laparoscopy for primary rectal cancer is associated with a greater number of LN as well as short-term benefits. Tumors in the upper rectum are associated with a higher number of LN than those in the mid and lower rectum. The type of surgery had no effect on lymph node yield either. Tumors with complete or almost complete pathologic regression were exactly the ones with lower number of lymph nodes detected. Approximately one-third of patients with neoadjuvant treatment had less than 12 LN yield. CONCLUSION: The tumor regression grade is the most important factor for the decrease in the number of lymph nodes.

Ethylene response to pollen tube growth in Nicotiana tabacum flowers.

In flowers of Nicotiana tabacum L., pollination induces a transient increase in ethylene production by the pistil. The characteristic dynamics of the increase in ethylene correspond to the main steps of the pollen-tube journey into the pistil: penetration into the stigma, growth through the style, entry into the ovary and fertilization. Ethylene is synthesized de novo in the pistil, and its production is reduced in the dark. Ethylene production was monitored in tobacco flowers after pollination with incongruous pollen from three different Nicotiana species, N. rustica, N. repanda and N. trigonophylla, and with pollen from Petunia hybrida. Pollen from all of these different sources can germinate on the stigma surface but each pollen type shows a different behavior and efficiency in penetrating the pistil tissues. Thus, these different crosses provided a model with which to study the response of the pistil to pollination and fertilization. Ethylene evolution upon pollination in tobacco differed in each cross, suggesting that ethylene is correlated with the response to pollen tube growth in the tobacco flower.

Pre-reactive complexes in mixtures of water vapour with halogens: characterisation of H2O...ClF and H2O...F2 by a combination of rotational spectroscopy and ab initio calculations.

Complexes H2O...ClF and H2O...F2 were detected by means of their ground-state rotational spectra in mixtures of water vapour with chlorine monofluoride and difluorine, respectively. A fast-mixing nozzle was used in conjunction with a pulsed-jet, Fourier-transform microwave spectrometer to preclude the vigorous chemical reaction that these dihalogen species undergo with water. The ground-state spectra of seven isotopomers (H2 16O...35ClF, H2 16O...ClF, H2 18O...35ClF, D2 16O... 35ClF, D2 16O...37ClF, HDO...35ClF and HDO...37ClF) of the ClF complex and five isotopomers (H2O...F2, H2 18O...F2, D2O...F2, D2 18O...Fi and HDO...F2) of the F2 complex were analysed to yield rotational constants, quartic centrifugal distortion constants and nuclear hyperfine coupling constants. These spectroscopic constants were interpreted with the aid of simple models of the complexes to give effective geometries and intermolecular stretching force constants. Isotopic substitution showed that in each complex the H2O molecule acts as the electron donor and either CIF or F2 acts as the electron acceptor, with nuclei in the order H2O...ClF or H2O...F2. For H2O...ClF, the angle phi between the bisector of the HOH angle and the O...Cl internuclear line has the value 58.9(16)degrees, while the distance r(O...Cl)= 2.6081(23) A. The corresponding quantities for H2O...F2 are phi = 48.5(21)degrees and r(O...Fi) = 2.7480(27) A, where Fi indicates the inner F atom. The potential energy V(phi) as a function of the angle phi was obtained from ab initio calculations at the aug-cc-pVDZ/MP2 level of theory for each complex by carrying out geometry optimisations at fixed values of phi in the range +/-80degrees. The global minimum corresponded to a complex of Cs symmetry with a pyramidal configuration at O in each. The function V(phi) was of the double-minimum type in each case with equilibrium values phie = +/-55.8degrees and +/-40.5degrees for H2O...ClF and H2O...F2, respectively. The barrier at the planar C2v conformation was V0= 174cm(-1) for H2O...ClF and 7cm(-1) for H2O...F2. For the latter complex, the zero-point energy level lies above the top of the barrier.

[Trends in blood lead levels in the population of the city of Bologna]. / Andamento della piombemia nella popolazione della città di Bologna.

The aim of this study was to evaluate the blood lead levels in a sample of Bologna's population, 12 years after the previous screening campaign carried out in 1984. The investigated sample was divided, as in 1984, by age, sex, occupational exposure and selected life style factors. The blood lead levels presented a sharp reduction in comparison with the values observed in the previous study. In 1996, the 50 degrees, 90 degrees and 98 degrees percentile of blood lead were 50 micrograms/l, 90 micrograms/l and 140 micrograms/l whereas in 1984 they were 129 micrograms/l, 242 micrograms/l and 329 micrograms/l, respectively. Possibly, this result is related to a lower level of environmental lead pollution as a result of the increasing use of unleaded gasoline in new cars.

[Biological monitoring of lead in the study of urban pollution due to automobile traffic]. / Monitoraggio biologico del piombo nello studio dell'inquinamento urbano da traffico veicolare.

The Authors have reviewed the most important literature available on the determination of blood lead level in non-occupationally exposed subjects, children and groups exposed to vehicular traffic (i.e. policemen, bus drivers, etc.). They have also collected data concerning lead concentration in air (mcg/m3) and in gasoline (g/l). The results show that the gradual decrease of gasoline lead concentrations gives a consistent decrease of blood lead level in the general population. In Italy, in the nonoccupationally exposed subjects, the mean blood lead level in 1974 was 32 mcg/dl and in 1991 was 8,4 mcg/dl. The mean value in children is presently about 8,3 mcg/dl. The values in workers exposed to vehicular traffic are higher than those found in non-exposed population.

Benzene, an experimental multipotential carcinogen: results of the long-term bioassays performed at the Bologna Institute of Oncology.

In 1976, a systematic and integrated project of long-term carcinogenicity bioassays began at the Bentivoglio Experimental Unit of the Bologna Institute of Oncology. The Bologna experiments proved for the first time that benzene is an experimental carcinogen. These experiments demonstrated that benzene is carcinogenic when administered by ingestion and by inhalation and that it cause tumors in the various tested animal models (Sprague-Dawley rats, Wistar rats, Swiss mice, and RF/J mice). They also showed that benzene is a multipotential carcinogen, as it produces a variety of neoplasias in one or more of the tested animal models, including Zymbal gland carcinomas, carcinomas of the oral cavity, nasal cavities, skin, forestomach, and mammary glands, as well as angiosarcomas of the liver, hemolymphoreticular neoplasias, tumors of the lung, and possibly hepatomas. The Bologna experiments also indicated a clear-cut dose-response relationship in benzene carcinogenesis. This report presents the up-to-date results of the Bologna project. The need for more experimental research aimed at assessing the carcinogenic effects of low doses of benzene, of chemical mixtures containing benzene, and of benzene substitutes is emphasized. Also recommended are more comprehensive epidemiological investigations, extended to all types of malignancies, with particular regard to lung carcinomas.

Carcinogenicity of vinyl chloride in Sprague-Dawley rats after prenatal and postnatal exposure.

Vinyl chloride was administered by inhalation, 7 hours daily, 5 days weekly, at concentrations of 2500 and 0 ppm, to Sprague-Dawley rats. The treatment was started on 13-week-old breeders and male and female offspring (12-day embryos). The breeders and part of the offspring were exposed for 104 weeks; the other part of the offspring was exposed for 15 weeks only. Under the experimental conditions, vinyl chloride caused an exceptionally high incidence of brain neuroblastomas, liver angiosarcomas, and hepatocarcinomas. The age at start and/or length of treatment may affect the onset of these tumors in different ways.

Long-term carcinogenicity bioassay on vinylidene chloride administered by inhalation to Sprague-Dawley rats. New results.

Vinylidene chloride was administered by inhalation, 7 hours daily, 5 days weekly, at the concentration of 100 and 0 ppm, to Sprague-Dawley rats. The treatment was started on 13-week-old breeders, and male and female offspring (12-day embryos). The breeders and some of the offspring were exposed for 104 weeks; the other offspring were exposed for 15 weeks only. An increased incidence was found of malignant tumors and of leukemias, particularly in offspring treated for 104 weeks.

Long-term carcinogenicity bioassays on acrylonitrile administered by inhalation and by ingestion to Sprague-Dawley rats.

Sprague-Dawley rats were exposed to acrylonitrile by inhalation at 40, 20, 10, 5 and 0 ppm, 4 hours daily, 5 days weekly, for 52 weeks and at 60 ppm, 4-7 hours daily, 5 days weekly. The latter treatment was started on 13-week-old breeders, and male and female offspring (12-day-embryos). The breeders and part of the offspring were exposed for 104 weeks; the other part of the offspring was exposed for 15 weeks only. Sprague-Dawley rats were also exposed to acrylonitrile by ingestion (stomach tube), in olive oil, at 5 mg/kg b.w., once daily 3 times weekly for 52 weeks. Under the tested experimental conditions, acrylonitrile was shown to be carcinogenic in Sprague-Dawley rats when given by inhalation and did not produce any carcinogenic effect when given by ingestion. In the inhalation experiment, acrylonitrile caused an increase in different types of tumors and the most noticeable acrylonitrile-related tumor was encephalic glioma.

Long-term carcinogenicity bioassays on trichloroethylene administered by inhalation to Sprague-Dawley rats and Swiss and B6C3F1 mice.

Trichloroethylene was administered by inhalation, 7 hours daily, 5 days weekly, for 8 weeks, at concentrations of 600, 100 and 0 ppm, to Sprague-Dawley rats and Swiss mice; and for 104 weeks to Sprague-Dawley rats; and for 78 weeks to Swiss and B6C3F1 mice at concentrations of 600, 300, 100 and 0 ppm. The animals were kept under observation until spontaneous death. In the experiments reported herein, 3768 animals were studied. Under the experimental conditions, trichloroethylene appears to be carcinogenic in rats and mice (particularly in male Swiss mice). The most relevant finding was the dose-related increased incidence of Leydig cell tumors in male rats, and the onset of few renal tubuli adenocarcinomas at the highest dose, always in rats (4/130 males and 1/130 females). The renal tubuli adenocarcinomas were preceded by, and associated with, a characteristic lesion of the kidney: tubuli cell karyomegaly (megalonucleocytosis).

Long-term carcinogenicity bioassays on methylene chloride administered by ingestion to Sprague-Dawley rats and Swiss mice and by inhalation to Sprague-Dawley rats.

Methylene chloride was administered to Sprague-Dawley rats and Swiss mice by ingestion (stomach tube), in olive oil, at the doses of 500, 100 and 0 mg/kg body weight, once daily, 4-5 days weekly, for 64 weeks, and to Sprague-Dawley rats by inhalation, at the concentration of 100 and 0 ppm, 7 hours daily, for 5 days weekly. The inhalatory treatment was started on 13-week-old breeders, and male and female offspring (12-day embryos). The breeders and part of the offspring were exposed for 104 weeks; the other part of the offspring was exposed for 15 weeks only. The most important findings were: (1) the increased incidence of pulmonary tumors in male mice treated by ingestion at 500 mg/kg body weight; (2) a not-significant increase in total malignant tumors in rats exposed by inhalation at 100 ppm for 104 weeks; and (3) a not-significant increase in total malignant mammary tumors in female rats given methylene chloride by ingestion at 500 mg/kg body weight.

Experimental studies on benzene carcinogenicity at the Bologna Institute of Oncology: current results and ongoing research.

In 1977 Maltoni and Scarnato were the first to demonstrate that benzene is an experimental carcinogen in rats. With that and other experiments, Maltoni et al have shown that benzene administered by ingestion (stomach tube) or inhalation is a multipotential carcinogen in rats (of two different strains) and mice and produces a variety of tumors, namely: Zymbal gland carcinomas, oral and nasal cavity carcinomas, skin carcinomas, acanthomas, dysplasias and carcinomas of forestomach, mammary malignant tumors, hepatomas, liver angiosarcomas, hemolymphoreticular neoplasias, and pulmonary tumors. The incidence of Zymbal gland carcinomas and carcinomas of the oral and nasal cavities is affected by the length of treatment by inhalation and by the age of animals. However, the available epidemiological and experimental data at present do not provide precise information on the risk of doses around or below 10 ppm. Long-term carcinogenicity bioassays at 50, 25, 10, 5 and 1 ppm may be helpful for scientific risk assessment. In addition, these experiments have shown that toluene, xylene, and ethylbenzene, at high concentrations, cause an increase in the number of total malignant tumors.

Benzene: a multipotential carcinogen. Results of long-term bioassays performed at the Bologna Institute of Oncology.

Until recently, the incidence of benzene carcinogenicity was based only on the association between benzene occupational exposure and human leukemia, with many limited case reports and scanty epidemiological data. Available experimental studies up to 1976 on animals were rare, fragmentary, and inadequate, and had failed to prove the carcinogenic effects of benzenes. However, an integrated project of long-term carcinogenicity bioassays, begun in our laboratory in 1976 and still continuing, has shown that benzene produces a variety of tumors in rats including Zymbal gland carcinomas, carcinomas of the oral cavity, hepatocarcinomas, and possibly mammary carcinomas, lymphoreticular neoplasias, and other malignancies. Some of the tumors caused by benzene are uncommon or unusual in the breed of rats studied. Therefore benzene must be considered, under the studied experimental conditions, a strong multipotential carcinogen. The need for more experimental research is emphasized, particularly to assess the carcinogenic effects of low doses. Also recommended are more comprehensive epidemiological investigations, extended to all types of malignancies, and the application of adequate measures for primary prevention.